Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortium

Nikhil K Khankari; Harvey J Murff; Chenjie Zeng; Wanqing Wen; Rosalind A Eeles; Douglas F Easton; Zsofia Kote-Jarai; Ali Amin Al Olama; Sara Benlloch; Kenneth Muir; Graham G Giles; Fredrik Wiklund; Henrik Gronberg; Christopher A Haiman; Johanna Schleutker; Børge G Nordestgaard; Ruth C Travis; Jenny L Donovan; Nora Pashayan; Kay-Tee Khaw; Janet L Stanford; William J Blot; Stephen N Thibodeau; Christiane Maier; Adam S Kibel; Cezary Cybulski; Lisa Cannon-Albright; Hermann Brenner; Jong Park; Radka Kaneva; Jyotsna Batra; Manuel R Teixeira; Hardev Pandha; Wei Zheng; PRACTICAL consortium

doi:10.1038/bjc.2016.228

Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortium

Nikhil K Khankari, Harvey J Murff, Chenjie Zeng, Wanqing Wen, Rosalind A Eeles, Douglas F Easton, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, Kenneth Muir, Graham G Giles, Fredrik Wiklund, Henrik Gronberg, Christopher A Haiman, Johanna Schleutker, Børge G Nordestgaard, Ruth C Travis, Jenny L Donovan, Nora Pashayan, Kay-Tee KhawJanet L Stanford, William J Blot, Stephen N Thibodeau, Christiane Maier, Adam S Kibel, Cezary Cybulski, Lisa Cannon-Albright, Hermann Brenner, Jong Park, Radka Kaneva, Jyotsna Batra, Manuel R Teixeira, Hardev Pandha, Wei Zheng, PRACTICAL consortium

Department of Clinical Medicine

16 Citations (Scopus)

Abstract

Background:Prostate cancer is a common cancer worldwide with no established modifiable lifestyle factors to guide prevention. The associations between polyunsaturated fatty acids (PUFAs) and prostate cancer risk have been inconsistent. Using Mendelian randomisation, we evaluated associations between PUFAs and prostate cancer risk.Methods:We used individual-level data from a consortium of 22 721 cases and 23 034 controls of European ancestry. Externally-weighted PUFA-specific polygenic risk scores (wPRSs), with explanatory variation ranging from 0.65 to 33.07%, were constructed and used to evaluate associations with prostate cancer risk per one standard deviation (s.d.) increase in genetically-predicted plasma PUFA levels using multivariable-adjusted unconditional logistic regression.Results:No overall association was observed between the genetically-predicted PUFAs evaluated in this study and prostate cancer risk. However, risk reductions were observed for short-chain PUFAs, linoleic (OR LA =0.95, 95%CI=0.92, 0.98) and α-linolenic acids (OR ALA =0.96, 95%CI=0.93, 0.98), among men <62 years; whereas increased risk was found among men ≥62 years for LA (OR LA =1.04, 95%CI=1.01, 1.07). For long-chain PUFAs (i.e., arachidonic, eicosapentaenoic, and docosapentaenoic acids), increased risks were observed among men <62 years (OR AA =1.05, 95%CI=1.02, 1.08; OR EPA =1.04, 95%CI=1.01, 1.06; OR DPA =1.05, 95%CI=1.02, 1.08).Conclusion:Results from this study suggest that circulating ω-3 and ω-6 PUFAs may have a different role in the aetiology of early- and late-onset prostate cancer.

Original language	English
Journal	B J C
Volume	115
Issue number	5
Pages (from-to)	624-631
Number of pages	8
ISSN	0007-0920
DOIs	https://doi.org/10.1038/bjc.2016.228
Publication status	Published - 23 Aug 2016

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Khankari, N. K., Murff, H. J., Zeng, C., Wen, W., Eeles, R. A., Easton, D. F., Kote-Jarai, Z., Al Olama, A. A., Benlloch, S., Muir, K., Giles, G. G., Wiklund, F., Gronberg, H., Haiman, C. A., Schleutker, J., Nordestgaard, B. G., Travis, R. C., Donovan, J. L., Pashayan, N., ... PRACTICAL consortium (2016). Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortium. B J C, 115(5), 624-631. https://doi.org/10.1038/bjc.2016.228

Khankari, NK, Murff, HJ, Zeng, C, Wen, W, Eeles, RA, Easton, DF, Kote-Jarai, Z, Al Olama, AA, Benlloch, S, Muir, K, Giles, GG, Wiklund, F, Gronberg, H, Haiman, CA, Schleutker, J, Nordestgaard, BG, Travis, RC, Donovan, JL, Pashayan, N, Khaw, K-T, Stanford, JL, Blot, WJ, Thibodeau, SN, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Brenner, H, Park, J, Kaneva, R, Batra, J, Teixeira, MR, Pandha, H, Zheng, W & PRACTICAL consortium 2016, 'Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortium', B J C, vol. 115, no. 5, pp. 624-631. https://doi.org/10.1038/bjc.2016.228

@article{bb3b51c3d184482c8a06ba44df293562,

title = "Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortium",

abstract = "Background:Prostate cancer is a common cancer worldwide with no established modifiable lifestyle factors to guide prevention. The associations between polyunsaturated fatty acids (PUFAs) and prostate cancer risk have been inconsistent. Using Mendelian randomisation, we evaluated associations between PUFAs and prostate cancer risk.Methods:We used individual-level data from a consortium of 22 721 cases and 23 034 controls of European ancestry. Externally-weighted PUFA-specific polygenic risk scores (wPRSs), with explanatory variation ranging from 0.65 to 33.07%, were constructed and used to evaluate associations with prostate cancer risk per one standard deviation (s.d.) increase in genetically-predicted plasma PUFA levels using multivariable-adjusted unconditional logistic regression.Results:No overall association was observed between the genetically-predicted PUFAs evaluated in this study and prostate cancer risk. However, risk reductions were observed for short-chain PUFAs, linoleic (OR LA =0.95, 95%CI=0.92, 0.98) and α-linolenic acids (OR ALA =0.96, 95%CI=0.93, 0.98), among men <62 years; whereas increased risk was found among men ≥62 years for LA (OR LA =1.04, 95%CI=1.01, 1.07). For long-chain PUFAs (i.e., arachidonic, eicosapentaenoic, and docosapentaenoic acids), increased risks were observed among men <62 years (OR AA =1.05, 95%CI=1.02, 1.08; OR EPA =1.04, 95%CI=1.01, 1.06; OR DPA =1.05, 95%CI=1.02, 1.08).Conclusion:Results from this study suggest that circulating ω-3 and ω-6 PUFAs may have a different role in the aetiology of early- and late-onset prostate cancer.",

author = "Khankari, {Nikhil K} and Murff, {Harvey J} and Chenjie Zeng and Wanqing Wen and Eeles, {Rosalind A} and Easton, {Douglas F} and Zsofia Kote-Jarai and {Al Olama}, {Ali Amin} and Sara Benlloch and Kenneth Muir and Giles, {Graham G} and Fredrik Wiklund and Henrik Gronberg and Haiman, {Christopher A} and Johanna Schleutker and Nordestgaard, {B{\o}rge G} and Travis, {Ruth C} and Donovan, {Jenny L} and Nora Pashayan and Kay-Tee Khaw and Stanford, {Janet L} and Blot, {William J} and Thibodeau, {Stephen N} and Christiane Maier and Kibel, {Adam S} and Cezary Cybulski and Lisa Cannon-Albright and Hermann Brenner and Jong Park and Radka Kaneva and Jyotsna Batra and Teixeira, {Manuel R} and Hardev Pandha and Wei Zheng and {PRACTICAL consortium}",

year = "2016",

month = aug,

day = "23",

doi = "10.1038/bjc.2016.228",

language = "English",

volume = "115",

pages = "624--631",

journal = "The British journal of cancer. Supplement",

issn = "0007-0920",

publisher = "nature publishing group",

number = "5",

}

TY - JOUR

T1 - Polyunsaturated fatty acids and prostate cancer risk

T2 - a Mendelian randomisation analysis from the PRACTICAL consortium

AU - Khankari, Nikhil K

AU - Murff, Harvey J

AU - Zeng, Chenjie

AU - Wen, Wanqing

AU - Eeles, Rosalind A

AU - Easton, Douglas F

AU - Kote-Jarai, Zsofia

AU - Al Olama, Ali Amin

AU - Benlloch, Sara

AU - Muir, Kenneth

AU - Giles, Graham G

AU - Wiklund, Fredrik

AU - Gronberg, Henrik

AU - Haiman, Christopher A

AU - Schleutker, Johanna

AU - Nordestgaard, Børge G

AU - Travis, Ruth C

AU - Donovan, Jenny L

AU - Pashayan, Nora

AU - Khaw, Kay-Tee

AU - Stanford, Janet L

AU - Blot, William J

AU - Thibodeau, Stephen N

AU - Maier, Christiane

AU - Kibel, Adam S

AU - Cybulski, Cezary

AU - Cannon-Albright, Lisa

AU - Brenner, Hermann

AU - Park, Jong

AU - Kaneva, Radka

AU - Batra, Jyotsna

AU - Teixeira, Manuel R

AU - Pandha, Hardev

AU - Zheng, Wei

AU - PRACTICAL consortium

PY - 2016/8/23

Y1 - 2016/8/23

N2 - Background:Prostate cancer is a common cancer worldwide with no established modifiable lifestyle factors to guide prevention. The associations between polyunsaturated fatty acids (PUFAs) and prostate cancer risk have been inconsistent. Using Mendelian randomisation, we evaluated associations between PUFAs and prostate cancer risk.Methods:We used individual-level data from a consortium of 22 721 cases and 23 034 controls of European ancestry. Externally-weighted PUFA-specific polygenic risk scores (wPRSs), with explanatory variation ranging from 0.65 to 33.07%, were constructed and used to evaluate associations with prostate cancer risk per one standard deviation (s.d.) increase in genetically-predicted plasma PUFA levels using multivariable-adjusted unconditional logistic regression.Results:No overall association was observed between the genetically-predicted PUFAs evaluated in this study and prostate cancer risk. However, risk reductions were observed for short-chain PUFAs, linoleic (OR LA =0.95, 95%CI=0.92, 0.98) and α-linolenic acids (OR ALA =0.96, 95%CI=0.93, 0.98), among men <62 years; whereas increased risk was found among men ≥62 years for LA (OR LA =1.04, 95%CI=1.01, 1.07). For long-chain PUFAs (i.e., arachidonic, eicosapentaenoic, and docosapentaenoic acids), increased risks were observed among men <62 years (OR AA =1.05, 95%CI=1.02, 1.08; OR EPA =1.04, 95%CI=1.01, 1.06; OR DPA =1.05, 95%CI=1.02, 1.08).Conclusion:Results from this study suggest that circulating ω-3 and ω-6 PUFAs may have a different role in the aetiology of early- and late-onset prostate cancer.

AB - Background:Prostate cancer is a common cancer worldwide with no established modifiable lifestyle factors to guide prevention. The associations between polyunsaturated fatty acids (PUFAs) and prostate cancer risk have been inconsistent. Using Mendelian randomisation, we evaluated associations between PUFAs and prostate cancer risk.Methods:We used individual-level data from a consortium of 22 721 cases and 23 034 controls of European ancestry. Externally-weighted PUFA-specific polygenic risk scores (wPRSs), with explanatory variation ranging from 0.65 to 33.07%, were constructed and used to evaluate associations with prostate cancer risk per one standard deviation (s.d.) increase in genetically-predicted plasma PUFA levels using multivariable-adjusted unconditional logistic regression.Results:No overall association was observed between the genetically-predicted PUFAs evaluated in this study and prostate cancer risk. However, risk reductions were observed for short-chain PUFAs, linoleic (OR LA =0.95, 95%CI=0.92, 0.98) and α-linolenic acids (OR ALA =0.96, 95%CI=0.93, 0.98), among men <62 years; whereas increased risk was found among men ≥62 years for LA (OR LA =1.04, 95%CI=1.01, 1.07). For long-chain PUFAs (i.e., arachidonic, eicosapentaenoic, and docosapentaenoic acids), increased risks were observed among men <62 years (OR AA =1.05, 95%CI=1.02, 1.08; OR EPA =1.04, 95%CI=1.01, 1.06; OR DPA =1.05, 95%CI=1.02, 1.08).Conclusion:Results from this study suggest that circulating ω-3 and ω-6 PUFAs may have a different role in the aetiology of early- and late-onset prostate cancer.

U2 - 10.1038/bjc.2016.228

DO - 10.1038/bjc.2016.228

M3 - Journal article

C2 - 27490808

SN - 0007-0920

VL - 115

SP - 624

EP - 631

JO - The British journal of cancer. Supplement

JF - The British journal of cancer. Supplement

IS - 5

ER -

Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortium

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